These comments address
the Advanced Notice of Public Rulemaking on concerning the standards to
be applied for accepting intentional dosing studies of human subjects.
They are submitted on behalf of Farmworker Justice Fund Inc.

The Farmworker Justice
Fund Inc. (FJF) is a nonprofit organization, based in Washington D.C.,
which is dedicated to improving the living and working conditions of migrant
and seasonal farmworkers throughout the nation. Throughout its 21-year
history, FJF has advocated for policies which would increase protections
for farmworkers from exposure to toxic pesticides.

The U.S. Environmental
Protection Agency (EPA) has asked for public comment on a multiplicity
of questions to assist it in determining whether and under what circumstances
and subject to what standards, the EPA should accept, consider and rely
on studies involving the intentional dosing of human subjects with pesticides
or other toxic environmental agents.

We urge the EPA

(1) to categorically
reject any study using the intentional, non-therapeutic dosing of human
subjects with toxic pesticides for the primary purpose of establishing
a No Observeable Adverse Effect Level (NOAEL) or a No Observeaable Effect
Level (NOEL) on the grounds that any such study is unethical and inconsistent
with accepted national and international legal standards;
(2) to determine that it will not accept, consider or continue to rely
upon the previously submitted human subject studies for purposes of setting
pesticide NOAEL/NOELs because they are scientifically and ethically flawed
and do not meet applicable legal standards; and
(3) The EPA should only accept, consider or rely upon a Third Party study
or Agency-supported research, using the intentional dosing of human subjects,
in limited circumstances where (i) the principles established by the Common
Rule and other nationally and internationally recognized ethical standards
are met; (ii) the data to be derived is essential and adequate data could
not be obtained from other sources' and (iii)the resulting data will have
adequate statistical power to provide useful information concerning our
highly diverse population, including those who are most vulnerable (e.g.,
fetuses, infants, children, adolescents, pregnant women, the elderly and
those with compromised immune systems)..

Prior to the publication
of the ANPR, the EPA had convened a Joint Subcommittee of its Science
Advisory Board (SAB) and the FIFRA Scientific Advisory Panel (SAP). In
a Report entitled Comments on the Use of Data from the Testing of Human
Subjects (SAB/SAP Report), the Joint SAB/SAP Subcommittee found, nter
alia, that the intentional testing of pesticides on human subjects should
be subject to limitations "ranging from 'rigorous' to 'severe,' that
such studies should not be conducted if data is available from other sources
(e.g., animal studies, models or unintentional human exposures) or if
the resulting data will lack adequate statistical power and that such
studies should never involve children, pregnant women or other vulnerable
populations.. SAB/SAP Report at 3. Further, the SAB/SAP Report stated
that the "Subcommittee, in general, would not support human experimentation
primarily to determine a No Observeable Adverse Effect Level." (SAB/SAP
Report at 11). While we do not endorse all of the Majority Report's findings,
these conclusions of the Joint SAB/SAP Committee are sound and should
be adopted by EPA..

The ethical concerns
raised by the intentionalnontherapeutic testing of toxic pesticides on
human subjects should be informed by the international and national standards
established to regulate human experimentation of these kinds. The applicable
standards include: 1) The Nuremberg Code, which was adopted by the United
States after revelations about the heinous Nazi experiments on humans,
conducted during World War II, came to light. It establishes minimum ethical
standards for human testing, which include the requirement that the study
be expected to "yield fruitful results for the good of society, unprocurable
by other methods or means of study." 2) The Helsinki Declaration,
which was adopted by the World Medical Association to govern medical testing
of humans. It requires, inter alia¸ that there be a "reasonable
likelihood" that the test subjects would benefit from the study.
3) FIFRA, which prohibits the "use [of] any pesticide in tests on
human beings unless such human beings (i) are fully informed of the nature
and purposes of the tests and of any physical and mental health consequences
which are reasonably foreseeable therefrom, and (ii) freely volunteer
to participate in the test." 4) The Common Rule, adopted by EPA at
40 CFR part 26, which in addition to requiring oversight by an Institutional
Review Board and the informed consent of participants, establishes the
principle that the "risks to subjects be reasonable in relation to
anticipated benefits, if any, to subjects, and the importance of the knowledge
that may reasonably be expected." 40 C.F.R. Part 26. Applying these
standards, it is clear that the EPA should establish a policy of refusing
to accept human studies for purposes of setting NOELs/NOAELs and that
it should refuse to accept or rely on the human studies which registrants
previously submitted to it for this purpose. In addition, the intentional
dosing of human subjects with pesticides should be allowed in very limited
circumstance to establish adequate protections for workers and handlers
who are occupationally exposed to pesticides.

I. THE TESTING
OF HUMANS TO ESTABLISH A NOEL/NOAEL IS ETHICALLY AND LEGALLY IMPROPER

Pesticides are poisons.
Many, like the neurotoxic organophosphate or n-methyl carbamate insecticides,
act on humans in much the same manner as they do on the insects they are
designed to kill. (Moses 1998) These compounds cause acute symptoms ranging
from nausea, headache, and dizziness, to convulsions, coma and death.
Some overexposure incidents with these chemicals lead to delayed neuropathy
and neuropsychological effects, including a loss of intellectual functioning.
(Savage 1988). Even at low exposure levels, some pesticide ingredients
may cause chemical sensitization or hormone disruption. Some pesticides
have also been associated with cancer, infertility, birth defects and
neurological disorders including Parkinson's Disease. (Moses 1998) These
data establish that exposure to pesticides is highly risky to human health.
In such circumstances, only the most compelling reasons could justify
the use of human test subjects.

The testing of human
subjects to establish a NOEL/NOAEL cannot meet this standard.

First, the human subjects
who bear the risk will not personally benefit from the results of the
study. Under both the Common Rule and the Helsinki Declaration, lack of
personal benefit would render the study unethical. Nor can the paltry
payment of $500 to $1,000 be viewed as an adequate benefit. While people
in desperate poverty (especially in the Third World) may be willing to
risk their health for such small sums, our society has already determined
that it is unacceptable to compromise health for mere financial gain.
For this reason, the sale of human organs is unlawful. Most testing of
pharmaceuticals is done on individuals who themselves suffer from the
condition to be alleviated by the drug under review. This is the type
of personal benefit, which is comencerate with the risk. Here there is
no benefit to the test subjects (and the EPA has alternate means of obtaining
adequate information on which to base its judgment). The only purpose
of these tests is to enable the pesticide manufacturers (i.e., the registrants)
to make it easier for themselves to register their products by reducing
applicable margins of safety. This is not the kind of benefit that could
justify the health risks involved. See SAB/SAP Report.

Second, the information
to be obtained is not of crucial importance to society and adequate information
can be secured by other less harmful means. See Nuremberg Code; Common
Rule, SAB/SAP Report. Far from being necessary, the EPA has for decades
established NOELs/NOAELs based primarily on animal studies without the
need for human studies. Moreover, supplemental data is often available
from case studies of unintentional human exposures and, where appropriate
computer models. In addition, the limited range of test subjects - usually
healthy young adults - will not provide useful information for evaluating
health effects on the highly diverse US population, especially the most
vulnerable subgroups of fetuses, infants, pregnant women, people with
compromised immune systems, the elderly etc. Thus, these studies cannot
be said to "yield fruitful results for the good of society, unprocurable
by other methods or means of study." Nuremberg Code.

Third, in conducting
these studies the companies cannot "fully inform" the test subjects
of the "reasonably foreseeable" health consequences. See FIFRA.
Studies to establish a NOEL/NOAEL are generally conducted at the beginning
of the toxicological test battery before the full range of short- and
long- term health effects have been established. Even now, however, many
pesticides which have been on the market for decades have not been fully
tested for chronic health effects. In addition, even though dozens of
pesticides have been identified as possible endocrine disruptors, scant
testing of this potential adverse effect has as yet been conducted. Moreover,
individual genetic make-up and metabolism, as well as a host of health
conditions, will make some individuals more susceptible to the toxic effects
of the pesticide - but the companies lack the information to identify
which individuals would be at risk. Similarly, the companies could not
fully inform potential test subjects of the potential adverse effects
the pesticide might cause in combination with medicines the person is
taking or other pesticides orchemicals to which the individual has been
exposed at home or work - because pesticide manufacturers rarely, if ever,
undertake experiments to determine the effects of their product in combination
with others. In these circumstances, it is not possible for the registrant
to provide full disclosure or obtain fully informed consent. As such,
these tests would not meet the requirements of FIFRA or the Common Rule.

Finally, it should
be noted that the companies are not seeking to use human subjects in the
pursuit of sound science. The questions that these tests would answer
are not the most important unknowns. As noted above, it would be far more
useful for the companies to use their resources to identify endocrine
disrupting effects at extremely low exposure levels, determine the effects
of pesticides in combination with each other, other chemicals or drugs,
establish clinical tests to determine when overexposure occurs, or conduct
epidemiological studies to determine the full extent of long term health
effects which are now experienced by people who have been overexposed
to their pesticide products. But these studies are not on the companies
agenda.

The studies previously
conducted are ethically, legally and scientifically flawed and should
not be considered by the EPA.

One of the guiding
principles established by FIFRA and the Common Rule is that human test
subjects must be fully informed of the health consequences and give informed
consent to participate. Numerous examples exist to show that the registrants
did not conduct these studies under conditions of informed consent. For
example, in a study conducted on azinphosmethyl, the substance to be tested
was sometimes referred to as a pesticide but other times referred to as
a drug. One study on chlorpyrifos recruited test subjects by claiming
that they would be advancing medical research. Nor did the consent forms
describe the potential for these organophosphate (OP) insecticides to
have long term effects, such as such as chemical sensitization, or neurobehavioral
effects or cancer - even though studies have associated OPs with each
of these conditions. In the absence of fully informed consent, the study
violates both applicable legal and ethical standards.

The studies that have
been conducted lack statistical power. Most concern dose groups of between
seven and 50 participants. By contrast, Professor Herbert Needleman of
the University of Pittsburgh, who was a member of the Joint SAB/SAP Subcommittee
noted, that thse studies should have had been 1,000 and 5,000 subjects.
Indeed, drug companies like Bayer normally use about 3,000 subjects when
they are doing a comparable clinical trial of a drug. Where the studies
lack scientific validity, they cannot pass ethical or legal muster. See
SAB/SAP Report, the Common Rule.

The human subject
studies done on organophosphates and n-methyl carbamates were unnecessary
because this information could be obtained in other ways. In addition
to the animal studies - which show the more significant effect of brain
cholinesterase inhibition - there are numerous studies of unintentional
exposure to these products which demonstrate human reactions at varying
dose levels.

In an article describing
a test of chlorpyrifos, conducted by MDS Harris Laboratories for then
Dow AgroSciences, a Dow spokesman was quoted as saying that previous research
guided the doses selected, so that they "would not cause any harm
to the volunteers." (Thompson 1999). But in the study itself, volunteers
suffered a variety of symptoms including nausea, shortness of breath,
and lack of sensation, which the researchers acknowledged were probably
or possibly due to the pesticide exposure. The companies'claim that they
try to avoid adverse health effects, is in essence, a tacit admission
that allowing people to suffer adverse health consequences - solely to
generate greater profits for chemical companies or growers - is not ethically
justifiable.

Finally, the EPA has
asked whether it may consider studies, which were conducted in the past
that do not meet current ethical and legal standards. The answer must
be a resounding no. When the companies conducted those studies they took
a risk that the studies would not be accepted. At least on two previous
occasions, during the tenure of EPA Administrator Lee Thomas and EPA Administrator
Carol Browner, the EPA has not accepted intentional nontherapeutic dosing
studies of human subjects. In addition, the standards established by the
Nuremberg Code predate any of the tests conducted so that the companies
should have known that their efforts did not meet internationally recognized
ethical requirements. Moreover, it has long been an established tenet
of American law that information obtained in violation of accepted standards
- like a confession obtained without Miranda warnings - cannot be used
because to do so would be to condone and encourage improper conduct. Similarly,
here, EPA use of studies conducted in violation of current ethical and
legal standards must be rejected.

III. Studies Conducted
with Pesticide Handlers or Field Workers to Determine the Extent of Needed
Protections Can Be Justified in Limited Circumstances

Studies conducted
on pesticide handlers or field workers to determine the extent of personal
protective equipment needed or the appropriate duration of a restricted
entry interval (REI) do not raise the same ethical and legal objections
as those conducted to set NOAEL/NOELs. Nonetheless, because they involve
the intentional exposure of people to toxins they should only be undertaken
in limited circumstances where they will provide essential information
which could not be adequately obtained by other means.

Studies conducted
on workers to determine the extent of protections needed may be permitted
for the following reaons: First, unlike the NOAEL/NOEL studies, the subjects
themselves are likely to benefit because they may be exposed to the pesticide
in the course of their work, and would benefit from having adequate protections
derived from the sudy results. Second, these studies are conducted after
the registrant has already conducted a full battery of tests on animals
to determine the full range of acute and chronic effects. This information
could be used to ensure that workers were not exposed to too great a dose
of the chemical and to provided volunteer subjects with information on
the reasonably foreseeable consequences of exposure to the product. Third,
the EPA itself has established guidelines for the conduct of studies,
so that the methodology has not been set solely by the company that stands
to benefit economically from a favorable result.

Nonetheless, there
are risks to the human subjects, because the companies will probably not
know which individuals are genetically or otherwise more susceptible to
the toxic effects of a pestide exposure. Nor will the product have been
tested in combination with other chemicals to which the volunteers are
routinely expoed in their homes or work. For that reason, when adequate
information can be obtained without human studies, human studies should
not be conducted.

IV. Additional
Observations

In response to other
questions posed by EPA we suggest the following additional guiding principles:

In no event should
intentional dosing of human subjects experiments be conducted on populations
that are not in a position to fully and voluntarily consent. This would
preclude the involvement of infants, children prisons, the mentally incapacitated
and those who work for the manufacturer or the testing organization.

When third party tests
are submitted the EPA should carefully review all aspects of the study,
including an evaluation of the participation of the Indepent Review Board
(IRV). From studies previously submitted it is apparent that such IRBs
may be "independent" in name only. Because IRBs, too, may stand
to benefit financially by approving a particular test protocol, the appropriateness
of the IRB's determinations, like every other aspect of the study design,
should be carefully reviewed to insure compliance with the Common Rule
and other applicable legal and ethical standards.

The EPA should not
accept the results of studies involving the intentional dosing of human
subjects unless it can determine that a study meets the current requirements
of the of Common Rule and other applicable legal and ethical standards.
If studies available in the open literature were not conducted in compliance
with these requirements, such studies should not be considered.

In applying legal
and ethical standards, the toxicity and range of adverse health effects
of a substance must be taken into account when evaluating the possible
benefit to the test subject and the appropriateness of the study. For
example, it would never be appropriate to intentionally dose a pregnant
woman with a product that might cause teratogenic effects. Nor would it
be ethical, given our current limited state of knowledge, to expose anyone
to a likely human carcinogen.

In no case should
developing humans (i.e., the fetus, infant, young children, or adolescents)
be exposed to toxic chemicals. There are currently too many unknown dangers
to justify such studies.

Finally, we have
attached several newspaper editorials condemning the human subject experimentation
for the purpose of setting pesticide NOAELs/NOELs.